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Conference Paper: The identification of sequence elements that mediate stabilization of the CHOP/Gadd153 mRNA by N-(4-hydroxyphenyl)retinamide (4HPR/fenretinide)
Title | The identification of sequence elements that mediate stabilization of the CHOP/Gadd153 mRNA by N-(4-hydroxyphenyl)retinamide (4HPR/fenretinide) |
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Authors | |
Issue Date | 2007 |
Publisher | American Association for Cancer Research. |
Citation | The 98th Annual Meeting of the American Association for Cancer Research (AACR 2007), Los Angeles, CA, 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, p. LB-200 How to Cite? |
Abstract | The CHOP, or the growth-arrest and DNA-damage-inducible gene (Gadd153) encodes a C/EBP-homologous protein that was previously shown to express in cultured cancer cells in response to the anticancer agent, N-(4-hydroxyphenyl)retinamide (4HPR or fenretinide). The 4HPR-induced expression of Gadd153 involves the stabilization of Gadd153 mRNA through a mechanism that is dependent on the production of reactive oxygen species. In this communication, we demonstrated by base-substitution and deletion analyses of the full-length Gadd153 cDNA that an adenylate-uridylate rich (AU-rich) element present in the 3’UTR of Gadd153 mRNA is essential for the mRNA-stabilization effect of 4HPR. However, a chimeric mRNA consisting of the 3’UTR of Gadd153 mRNA joined to the 3’-end of the coding sequence of green-fluorescent protein (GFP) was not stabilized. On the contrary, a similar chimeric mRNA consisting of the GFP coding sequence and a longer Gadd153 mRNA-fragment (containing the last 358 nucleotides of the Gadd153 coding sequence and the entire 3’UTR) was stabilized by 4HPR. These observations suggest that the AU-rich element in the 3’UTR of Gadd153 mRNA alone is not sufficient for 4HPR-induced mRNA stability. Examination of stability of mRNA species transcribed from various deletion and base-substituted mutants of Gadd153 cDNA revealed the presence of a 14-nucleotide sequence element (lying 39 nucleotides upstream of the last codon in the reading frame) that acted as a co-requisite sequence element for 4HPR-induced stability of Gadd153 mRNA. The deletion of sequences in between the 14-nucleotide sequence element and the AU-rich element did not affect 4HPR-induced stability of the resultant mRNA species. Our data demonstrate for the first time that the 4HPR-induced stability of Gadd153 mRNA is co-mediated by the AU-rich element and a novel sequence element of Gadd153 mRNA. Such a mechanism may be required for the sustained expression of Gadd153. |
Persistent Identifier | http://hdl.handle.net/10722/96656 |
ISSN | 2023 Impact Factor: 12.5 2023 SCImago Journal Rankings: 3.468 |
DC Field | Value | Language |
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dc.contributor.author | Lai, WL | en_HK |
dc.contributor.author | Wong, NS | en_HK |
dc.date.accessioned | 2010-09-25T16:40:37Z | - |
dc.date.available | 2010-09-25T16:40:37Z | - |
dc.date.issued | 2007 | en_HK |
dc.identifier.citation | The 98th Annual Meeting of the American Association for Cancer Research (AACR 2007), Los Angeles, CA, 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, p. LB-200 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | http://hdl.handle.net/10722/96656 | - |
dc.description.abstract | The CHOP, or the growth-arrest and DNA-damage-inducible gene (Gadd153) encodes a C/EBP-homologous protein that was previously shown to express in cultured cancer cells in response to the anticancer agent, N-(4-hydroxyphenyl)retinamide (4HPR or fenretinide). The 4HPR-induced expression of Gadd153 involves the stabilization of Gadd153 mRNA through a mechanism that is dependent on the production of reactive oxygen species. In this communication, we demonstrated by base-substitution and deletion analyses of the full-length Gadd153 cDNA that an adenylate-uridylate rich (AU-rich) element present in the 3’UTR of Gadd153 mRNA is essential for the mRNA-stabilization effect of 4HPR. However, a chimeric mRNA consisting of the 3’UTR of Gadd153 mRNA joined to the 3’-end of the coding sequence of green-fluorescent protein (GFP) was not stabilized. On the contrary, a similar chimeric mRNA consisting of the GFP coding sequence and a longer Gadd153 mRNA-fragment (containing the last 358 nucleotides of the Gadd153 coding sequence and the entire 3’UTR) was stabilized by 4HPR. These observations suggest that the AU-rich element in the 3’UTR of Gadd153 mRNA alone is not sufficient for 4HPR-induced mRNA stability. Examination of stability of mRNA species transcribed from various deletion and base-substituted mutants of Gadd153 cDNA revealed the presence of a 14-nucleotide sequence element (lying 39 nucleotides upstream of the last codon in the reading frame) that acted as a co-requisite sequence element for 4HPR-induced stability of Gadd153 mRNA. The deletion of sequences in between the 14-nucleotide sequence element and the AU-rich element did not affect 4HPR-induced stability of the resultant mRNA species. Our data demonstrate for the first time that the 4HPR-induced stability of Gadd153 mRNA is co-mediated by the AU-rich element and a novel sequence element of Gadd153 mRNA. Such a mechanism may be required for the sustained expression of Gadd153. | - |
dc.language | eng | en_HK |
dc.publisher | American Association for Cancer Research. | - |
dc.relation.ispartof | Cancer Research | en_HK |
dc.title | The identification of sequence elements that mediate stabilization of the CHOP/Gadd153 mRNA by N-(4-hydroxyphenyl)retinamide (4HPR/fenretinide) | en_HK |
dc.type | Conference_Paper | en_HK |
dc.identifier.email | Lai, WL: bennywll@hku.hk | en_HK |
dc.identifier.email | Wong, NS: nswong@hkucc.hku.hk | en_HK |
dc.identifier.authority | Wong, NS=rp00340 | en_HK |
dc.identifier.hkuros | 132446 | en_HK |
dc.identifier.volume | 67 | - |
dc.identifier.issue | 9S | - |
dc.identifier.spage | LB-200 | - |
dc.identifier.epage | LB-200 | - |
dc.identifier.issnl | 0008-5472 | - |